The research portion of this training is aimed at understanding how immunity is established in the lung. Increasing evidence ascribes a major role for lung dendritic cells (DC) in pulmonary immunity. However, the mechanism(s) of how this antigen presenting cell initiates primary immune responses after exposure to inhaled antigens is not completely understood. The major goal of the research proposal is to better understand how lung dendritic cells acquire and process antigen and develop into potent antigen presenting cells. Specifically, my research aims are designed to (a) determine whether DCs undergo maturational changes in vitro which affect their ability to acquire and process antigen for presentation to naive T cells, (b) determine if there are changes in the surface expression of accessory molecules and receptors, and invariant chain expression during in vitro culture, (c) determine whether cells in the lung milieu affect lung DCs maturation, and thus their phenotype and function, and (d) determine whether cytokines, shown to modulate the maturation of skin DCs, affect lung DCs maturation, and thus their phenotype and function. Achieving these research aims will aid in the development of more rational approaches to vaccination against pulmonary pathogens and the design of practical approaches to prevent manifestations of immunologically mediated lung diseases, such as asthma.